Prostate cancer is one of the most common malignancies in men with a reported incidence of 346,000 patients and approximately 87,000 deaths in Europe in 2006. It is the most common cancer diagnosis and the second leading cause of cancer related deaths in men in the United States. Because of the increasing sensitivity of prostate specific antigen (PSA) monitoring assays, prostate cancer is detected at an earlier and clinically localized stage, in which curative treatments like surgery and radiation can be performed. Nevertheless, these patients have a 10-60% chance of experiencing an asymptomatic increase of PSA within 10 years, known as a “biochemical relapse.” Biochemical relapse often indicates a hidden local recurrence of the cancer or the onset of still undetectable metastases.
Therapeutic options in this situation include external radiotherapy and androgen deprivation (also known as hormone ablation). However, neither therapeutic approach has been proven effective, especially with respect to prolonging the patient's long-term survival. Moreover, both treatments are hampered by a number of side effects, including the increased risk of cardiovascular difficulties, osteoporosis, weight gain, neurocognitive decline, development of urethral strictures, loss of libido and impotence, the risk of a reduction in skeletal calcium salts in terms of osteoporosis, and a markedly increased risk of pathologic bone fractures. In addition, there is some concern that androgen deprivation permits early development of androgen-independent neoplastic clones, ultimately resulting in further and faster long-term tumor progression. Moreover, the optimal timing for initiation of androgen deprivation therapy is debated, particularly for biochemical relapses characterized by low PSA values or long mean doubling times (DT's). Given these risks, both androgen deprivation therapy and external radiotherapy are of questionable therapeutic value for patients experiencing an early biochemical relapse.
Tumor associated antigens (“TAAs”) have been identified as potential cancer immunotherapeutic agents. Numerous TAAs specific for a variety of different tumor and tissue types have been identified, including those associated with the prostate. The identification of T-cells specific for TAAs in prostate tumor tissue, tumor-draining lymph nodes, and the peripheral circulatory system of cancer patients, as well as the increase of specific T-cell responses after immunotherapy, all suggest that manipulation of the immune system using TAAs could be useful in treating prostate cancer.
Various systems for in vivo antigenic presentation of prostate-specific TAAs have been tested in clinical trials, including: (1) vaccine therapy with autologous or allogeneic tumor cells; (2) autologous tumor cells engineered to express granulocyte-macrophage colony-stimulating factor; (3) dendritic cells pulsed ex vivo with HLA I and II-binding peptides; (4) tumor-mRNA transfected dendritic cells; and (5) recombinant vaccinia viruses expressing TAAs. However, most of these studies have been conducted in patients with androgen resistant prostate carcinoma. Little information is available about vaccination therapy in androgen-sensitive patients with a biochemical relapse prior to androgen deprivation therapy.
Therefore, new treatment options are needed for patients with prostate cancer, particularly patients with early biochemical relapse.